WO2007085470A3 - Cd19-specific immunotoxin and treatment method - Google Patents

Cd19-specific immunotoxin and treatment method Download PDF

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Publication number
WO2007085470A3
WO2007085470A3 PCT/EP2007/000683 EP2007000683W WO2007085470A3 WO 2007085470 A3 WO2007085470 A3 WO 2007085470A3 EP 2007000683 W EP2007000683 W EP 2007000683W WO 2007085470 A3 WO2007085470 A3 WO 2007085470A3
Authority
WO
WIPO (PCT)
Prior art keywords
protein
immunotoxin
modified
exotoxin
treatment method
Prior art date
Application number
PCT/EP2007/000683
Other languages
French (fr)
Other versions
WO2007085470A2 (en
Inventor
Georg H Fey
Matthias Peipp
Michael Schwemmlein
Original Assignee
Univ Friedrich Alexander Er
Georg H Fey
Matthias Peipp
Michael Schwemmlein
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Univ Friedrich Alexander Er, Georg H Fey, Matthias Peipp, Michael Schwemmlein filed Critical Univ Friedrich Alexander Er
Publication of WO2007085470A2 publication Critical patent/WO2007085470A2/en
Publication of WO2007085470A3 publication Critical patent/WO2007085470A3/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
    • A61K47/6817—Toxins
    • A61K47/6829—Bacterial toxins, e.g. diphteria toxins or Pseudomonas exotoxin A
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6849—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/04—Fusion polypeptide containing a localisation/targetting motif containing an ER retention signal such as a C-terminal HDEL motif

Abstract

An immunotoxin for use in, and a method for treating a subject having a cancer associated with malignant B- lineage cells or an autoimmune condition, are disclosed. The immunotoxin includes (a) an anti-CD19 antibody lacking an Fc fragment, (b) a modified exotoxin A protein having both Domains II and III, but lacking Domain I, and (c) a peptide linker joining the C-terminal end of the antibody to the N-terminal end of the modified exotoxin A protein. The linker is substantially resistant to extracellular cleavage. The modified exotoxin A protein may be further modified to include a C-terminal KDEL sequence (SEQ ID NO: 6) that promotes transport of the protein to the endoplasmic reticulum of cells that have taken up the immunotoxin.
PCT/EP2007/000683 2006-01-30 2007-01-26 Cd19-specific immunotoxin and treatment method WO2007085470A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US11/344,466 US20070178103A1 (en) 2006-01-30 2006-01-30 CD19-specific immunotoxin and treatment method
US11/344,466 2006-01-30

Publications (2)

Publication Number Publication Date
WO2007085470A2 WO2007085470A2 (en) 2007-08-02
WO2007085470A3 true WO2007085470A3 (en) 2007-10-11

Family

ID=38292950

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2007/000683 WO2007085470A2 (en) 2006-01-30 2007-01-26 Cd19-specific immunotoxin and treatment method

Country Status (3)

Country Link
US (1) US20070178103A1 (en)
TW (1) TW200738265A (en)
WO (1) WO2007085470A2 (en)

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2006262232A1 (en) 2005-06-20 2007-01-04 Medarex, Inc. CD19 antibodies and their uses
AU2007272224B2 (en) * 2006-07-10 2013-05-02 Novartis Ag scFv antibodies which pass epithelial and/or endothelial layers
SI2059536T1 (en) 2006-08-14 2014-06-30 Xencor, Inc. Optimized antibodies that target cd19
KR101456728B1 (en) 2006-09-08 2014-10-31 메디뮨 엘엘씨 Humanized anti-cd19 antibodies and their use in treatment of oncology, transplantation and autoimmune disease
EP2211904B1 (en) 2007-10-19 2016-08-17 Seattle Genetics, Inc. Cd19 binding agents and uses thereof
CA2705289A1 (en) * 2007-11-13 2009-05-22 The Scripps Research Institute Production of cytotoxic antibody-toxin fusion in eukaryotic algae
EP2261258A1 (en) * 2009-06-08 2010-12-15 Schuler, Gerold MCSP-aligned scFv antibody fragments and use of same
EP2600901B1 (en) 2010-08-06 2019-03-27 ModernaTX, Inc. A pharmaceutical formulation comprising engineered nucleic acids and medical use thereof
ES2737960T3 (en) 2010-10-01 2020-01-17 Modernatx Inc Nucleosides, nucleotides and modified nucleic acids and their uses
AU2012236099A1 (en) 2011-03-31 2013-10-03 Moderna Therapeutics, Inc. Delivery and formulation of engineered nucleic acids
KR20140033391A (en) 2011-06-09 2014-03-18 더 유나이티드 스테이츠 오브 어메리카, 애즈 리프리젠티드 바이 더 세크러테리, 디파트먼트 오브 헬쓰 앤드 휴먼 서비씨즈 Pseudomonas exotoxin a with less immunogenic t cell and/or b cell epitopes
US9464124B2 (en) 2011-09-12 2016-10-11 Moderna Therapeutics, Inc. Engineered nucleic acids and methods of use thereof
AU2012308591B2 (en) 2011-09-16 2017-02-23 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Pseudomonas exotoxin a with less immunogenic B cell epitopes
EP3682905B1 (en) 2011-10-03 2021-12-01 ModernaTX, Inc. Modified nucleosides, nucleotides, and nucleic acids, and uses thereof
EP2791160B1 (en) 2011-12-16 2022-03-02 ModernaTX, Inc. Modified mrna compositions
US9572897B2 (en) 2012-04-02 2017-02-21 Modernatx, Inc. Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins
US9283287B2 (en) 2012-04-02 2016-03-15 Moderna Therapeutics, Inc. Modified polynucleotides for the production of nuclear proteins
AU2013243948A1 (en) 2012-04-02 2014-10-30 Moderna Therapeutics, Inc. Modified polynucleotides for the production of proteins associated with human disease
US9303079B2 (en) 2012-04-02 2016-04-05 Moderna Therapeutics, Inc. Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins
US9512456B2 (en) 2012-08-14 2016-12-06 Modernatx, Inc. Enzymes and polymerases for the synthesis of RNA
EP4074834A1 (en) 2012-11-26 2022-10-19 ModernaTX, Inc. Terminally modified rna
US8980864B2 (en) 2013-03-15 2015-03-17 Moderna Therapeutics, Inc. Compositions and methods of altering cholesterol levels
WO2015048744A2 (en) 2013-09-30 2015-04-02 Moderna Therapeutics, Inc. Polynucleotides encoding immune modulating polypeptides
CA2926218A1 (en) 2013-10-03 2015-04-09 Moderna Therapeutics, Inc. Polynucleotides encoding low density lipoprotein receptor
WO2020058749A1 (en) * 2018-09-20 2020-03-26 Universita' Degli Studi Di Pavia An antibody drug fusion based on asparaginase

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996005865A1 (en) * 1994-08-22 1996-02-29 Regents Of The University Of Minnesota Combination immunotoxin/antineoplastic agent therapy for b-lineage cancer
WO2000067796A1 (en) * 1999-05-07 2000-11-16 Genentech, Inc. Treatment of autoimmune diseases with antagonists which bind to b cell surface markers
WO2003051926A2 (en) * 2001-12-14 2003-06-26 Friedrich-Alexander-Universitaet Erlangen-Nuernberg Anti-cd7 immunotoxin as fusion protein
WO2007014743A2 (en) * 2005-07-29 2007-02-08 Friedrich-Alexander-Universität Erlangen-Nürnberg Cd33-specific single-chain immunotoxin and method of use

Family Cites Families (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4816567A (en) * 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
US5225539A (en) * 1986-03-27 1993-07-06 Medical Research Council Recombinant altered antibodies and methods of making altered antibodies
GB8823869D0 (en) * 1988-10-12 1988-11-16 Medical Res Council Production of antibodies
US5530101A (en) * 1988-12-28 1996-06-25 Protein Design Labs, Inc. Humanized immunoglobulins
US5633426A (en) * 1990-05-25 1997-05-27 Systemix, Inc. In vivo use of human bone marrow for investigation and production
US5545806A (en) * 1990-08-29 1996-08-13 Genpharm International, Inc. Ransgenic non-human animals for producing heterologous antibodies
ES2108048T3 (en) * 1990-08-29 1997-12-16 Genpharm Int PRODUCTION AND USE OF LOWER TRANSGENIC ANIMALS CAPABLE OF PRODUCING HETEROLOGICAL ANTIBODIES.
US5625126A (en) * 1990-08-29 1997-04-29 Genpharm International, Inc. Transgenic non-human animals for producing heterologous antibodies
US5789650A (en) * 1990-08-29 1998-08-04 Genpharm International, Inc. Transgenic non-human animals for producing heterologous antibodies
US5661016A (en) * 1990-08-29 1997-08-26 Genpharm International Inc. Transgenic non-human animals capable of producing heterologous antibodies of various isotypes
US5874299A (en) * 1990-08-29 1999-02-23 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5877397A (en) * 1990-08-29 1999-03-02 Genpharm International Inc. Transgenic non-human animals capable of producing heterologous antibodies of various isotypes
US5770429A (en) * 1990-08-29 1998-06-23 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5814318A (en) * 1990-08-29 1998-09-29 Genpharm International Inc. Transgenic non-human animals for producing heterologous antibodies
US5686072A (en) * 1992-06-17 1997-11-11 Board Of Regents, The University Of Texas Epitope-specific monoclonal antibodies and immunotoxins and uses thereof
JPH11513669A (en) * 1995-10-13 1999-11-24 アメリカ合衆国 Immunotoxins containing disulfide-stabilized antibody fragments
PT1071700E (en) * 1998-04-20 2010-04-23 Glycart Biotechnology Ag Glycosylation engineering of antibodies for improving antibody-dependent cellular cytotoxicity
CA2279474C (en) * 1998-07-31 2011-01-04 Stemcell Technologies Inc. Novel antibody composition for debulking blood and bone marrow samples from cml patients
US20040136908A1 (en) * 2001-04-09 2004-07-15 Olson William C. Anti-cd19 immunotoxins
AU2006214121B9 (en) * 2005-02-15 2013-02-14 Duke University Anti-CD19 antibodies and uses in oncology

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996005865A1 (en) * 1994-08-22 1996-02-29 Regents Of The University Of Minnesota Combination immunotoxin/antineoplastic agent therapy for b-lineage cancer
WO2000067796A1 (en) * 1999-05-07 2000-11-16 Genentech, Inc. Treatment of autoimmune diseases with antagonists which bind to b cell surface markers
WO2003051926A2 (en) * 2001-12-14 2003-06-26 Friedrich-Alexander-Universitaet Erlangen-Nuernberg Anti-cd7 immunotoxin as fusion protein
WO2007014743A2 (en) * 2005-07-29 2007-02-08 Friedrich-Alexander-Universität Erlangen-Nürnberg Cd33-specific single-chain immunotoxin and method of use

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
BEJCEK B E ET AL: "DEVELOPMENT AND CHARACTERIZATION OF THREE RECOMBINANT SINGLE CHAIN ANTIBODY FRAGMENTS (SCFVS) DIRECTED AGAINST THE CD19 ANTIGEN", CANCER RESEARCH, AMERICAN ASSOCIATION FOR CANCER RESEARCH, BALTIMORE, MD, US, vol. 55, no. 11, 1 June 1995 (1995-06-01), pages 2346 - 2351, XP002019021, ISSN: 0008-5472 *
MEEKER T C ET AL: "A unique human B lymphocyte antigen defined by a monoclonal antibody", HYBRIDOMA, LIEBERT, NEW YORK, NY, US, vol. 3, no. 4, 1984, pages 305 - 320, XP009086320, ISSN: 0272-457X *
SCHWEMMLEIN M ET AL: "A CD19-specific single-chain immunotoxin mediates potent apoptosis of B-lineage leukemic cells.", LEUKEMIA : OFFICIAL JOURNAL OF THE LEUKEMIA SOCIETY OF AMERICA, LEUKEMIA RESEARCH FUND, U.K JUL 2007, vol. 21, no. 7, 10 May 2007 (2007-05-10), pages 1405 - 1412, XP002445346, ISSN: 0887-6924 *
SCHWEMMLEIN MICHAEL ET AL: "A CD33-SPECIFIC SINGLE-CHAIN IMMUNOTOXIN MEDIATES POTENT APOPTOSIS OF CULTURED HUMAN MYELOID LEUKAEMIA CELLS", BRITISH JOURNAL OF HAEMATOLOGY, OXFORD, GB, vol. 133, no. 2, April 2006 (2006-04-01), pages 141 - 151, XP009080463, ISSN: 0007-1048 *
SEETHARAM S ET AL: "INCREASED CYTOTOXIC ACTIVITY OF PSEUDOMONAS EXOTOXIN AND TWO CHIMERIC TOXINS ENDING IN KDEL", JOURNAL OF BIOLOGICAL CHEMISTRY, AMERICAN SOCIETY OF BIOLOCHEMICAL BIOLOGISTS, BIRMINGHAM,, US, vol. 266, no. 26, 15 September 1991 (1991-09-15), pages 17376 - 17381, XP000918998, ISSN: 0021-9258 *
WANG D ET AL: "Generation and characterization of an anti-CD19 single-chain Fv immunotoxin composed of C-terminal disulfide-linked dgRTA.", BIOCONJUGATE CHEMISTRY 1997 NOV-DEC, vol. 8, no. 6, November 1997 (1997-11-01), pages 878 - 884, XP002445345, ISSN: 1043-1802 *

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Publication number Publication date
WO2007085470A2 (en) 2007-08-02
TW200738265A (en) 2007-10-16
US20070178103A1 (en) 2007-08-02

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